Gary L. Davis

Hepatocellular carcinoma: management of an increasingly common problem

Hepatocellular carcinoma (HCC) is a common cancer that typically occurs in the setting of cirrhosis and chronic hepatitis virus infections. Hepatitis B and C account for approximately 80% of cases worldwide. HCC is currently the fifth most common malignancy in men and the eighth in women worldwide; its incidence is increasing dramatically in many parts of the world. Recognition of those at risk and early diagnosis by surveillance with imaging, with or without serologic testing, are extremely important. Many highly effective and even curative therapies are now available and include resection, liver transplantation, and local ablation. Appropriate application of these interventions offers hope of prolonged survival to many patients with this otherwise lethal complication of liver disease.

Alpha fetoprotein, ultrasound, computerized tomography and magnetic resonance imaging for detection of hepatocellular carcinoma in patients with advanced cirrhosis

Backgroundu2002 Serum alpha fetoprotein (AFP), ultrasound, computerized tomography scanning, and magnetic resonance imaging are commonly used to screen for hepatocellular carcinoma (HCC) in patients with cirrhosis.

Improved results of transplantation for hepatocellular carcinoma: A report from the international registry of hepatic tumors in liver transplantation

Improved outcome after liver transplantation (LTX) for hepatocellular carcinoma (HCC) made LTX a legitimate treatment of the disease. We analyzed trends of LTX for HCC with tumors known before transplantation in 902 patients in a large international registry across 3 periods: 1983–1990, 1991–1996, and 1997–2005. Patient survival improved gradually across eras, with 5‐year survival rates of 25.3%, 44.4%, and 67.8%, respectively (P < 0.0001), and the 5‐year tumor recurrence rate declined from 59% to 41.3% and 15%, respectively (P < 0.0001). The number of HCC nodules and tumor size decreased over time, and there were fewer moderately or poorly differentiated tumors. Tumors > 5 cm decreased from 54.5% to 31.7% and 11.7%, respectively (P < 0.0001), and LTX with ≥4 nodules decreased from 38.9% to 23.5% and 15.1%, respectively (P = 0.0044). Poorly differentiated tumors decreased from 37.2% to 31.8% and 20.3%, respectively (P = 0.0005). Tumor microvascular invasion remained at 21.2% to 23.8% despite changes in patient selection over time (P = 0.7124). Stepwise Cox regression analysis (n = 502) showed significant risk for tumor recurrence and patient survival for transplants before 1997 [hazard ratio (HR), 1.82 and 1.88, respectively], tumor size > 6 cm (HR, 2.09 and 1.76), microvascular invasion (HR, 1.75 and 1.69, respectively), and alpha‐fetoprotein > 200 (HR, 2.45 and 2.32, respectively). In conclusion, outcome after LTX for HCC has improved continuously over the past 20 years. Improved perioperative care and better patient selection may partially explain the improved outcome after LTX for HCC. Liver Transpl 15:574–580, 2009.

Long-term follow-up of liver transplantation for Budd-Chiari syndrome with antithrombotic therapy based on the etiology.

Background. Because myeloproliferative disorders (MPDs) are a frequent cause of Budd-Chiari syndrome (BCS), treatment directed toward altering platelet production and function may be more rational and effective than anticoagulation after liver transplantation. Methods. We reviewed data on 25 patients who received liver transplantation for BCS at our institution from 1987 to 2007. Posttransplant antithrombotic treatment was based on the cause of BCS: 17 patients with MPDs received hydroxyurea/aspirin; 5 received warfarin; and 3 (2 whose hypercoagulable disorder was corrected and 1 with sarcoidosis) received no therapy. Results. Both graft survival (88% at 5 years) and patient survival (92% at 5 years) were superior in the BCS group compared with the 2609 patients who received liver transplants for other indications. Vascular complications included three instances of hepatic artery stenosis (NS compared with non-BCS liver recipients), one of portal vein thrombosis (nonsignificant [NS]), and one of portal vein stenosis (NS). All 25 patients underwent multiple liver biopsies with no bleeding complications. Conclusions. Using hydroxyurea and aspirin to treat patients with BCS caused by an MPD seems to be safe and effective and avoids the risks of anticoagulation with warfarin.

Post-liver transplant survival in hepatitis C patients is improving over time.

Outcomes after orthotopic liver transplantation for chronic hepatitis C have been reported to be worsening over the last 2 decades. We analyzed our centers experience over 15 years to identify trends in post–orthotopic liver transplantation survival in patients with and without hepatitis C virus infection. Patient survival and graft survival among adult primary orthotopic liver transplantation recipients who survived more than 90 days from January 1991 to June 2006 at the Baylor Regional Transplant Institute (n = 1901) were evaluated by Kaplan‐Meier analysis. Those with or without hepatitis C virus infection were analyzed by era: era 1, 1991‐1994 (n = 473); era 2, 1995‐1998 (n = 421); era 3, 1999‐2002 (n = 498); and era 4, 2003‐2006 (n = 512). Differences in eras with disparate survivals were assessed by univariate and multivariable analysis. Overall, patient survival and graft survival were significantly lower among hepatitis C virus infection recipients compared to those without hepatitis C virus infection (P < 0.001). This difference was dependent on the era of transplantation, with progressive improvement in hepatitis C virus patient (P < 0.001) and graft (P < 0.001) survival in sequential eras. Several factors accounted for this improvement, notably better selection of hepatocellular carcinoma patients and fewer late cytomegalovirus infections. Improvement occurred despite an increase in the ages of both donors and recipients. In conclusion, posttransplant survival after orthotopic liver transplantation for chronic hepatitis C has improved significantly over the last 15 years despite demographic changes in patients and grafts that have been previously shown to impair survival. A major reason for this improvement is better selection of patients with concurrent hepatocellular carcinoma and fewer late cytomegalovirus infections, although other factors may play a role as well. Liver Transpl 15:360–368, 2009.

Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma (HCC) and cirrhosis. This study was conducted to determine the impact of pre‐transplant locoregional therapy (LRT) on HCC and our institutions experience with expansion to United Network of Organ Sharing Region 4 T3 (R4T3) criteria. Two hundred and twenty‐five patients with HCC (176 meeting Milan and 49 meeting R4T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4T3 criteria displayed less favorable biological features such as higher median alpha‐fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five‐yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre‐transplant LRT did not affect post‐transplant outcomes in patients meeting Milan criteria but did result in lower three‐yr HCC recurrence (7% vs. 75%, p < 0.001) and better three‐yr survival (p = 0.02) in patients meeting R4T3 criteria. Tumor biology and pre‐transplant LRT are important factors that determine the post‐transplant outcomes in patients with HCC who meet R4T3 criteria.

Inferior Vena Cava Stent Resolves Hepatopulmonary Syndrome in an Adult with a Spontaneous Inferior Vena Cava-Portal Vein Shunt

Hepatic encephalopathy and hepatopulmonary syndrome are classically seen in patients with cirrhosis and hepatic synthetic dysfunction. However, they can be caused by vascular anomalies that shunt blood away from the liver. In these settings, the vascular anomalies most often require surgical correction or liver transplantation. However, we report a case of a 43-year-old male with hepatic encephalopathy and hepatopulmonary syndrome from a type 2 Abernethy malformation that was corrected with an inferior vena cava (IVC) stent.

Effect of tacrolimus on survival in hepatitis C–infected patients after liver transplantation

The observation that cyclosporine inhibits HCV replication in vitro has led some programs to use cyclosporine as the calcineurin inhibitor (CNI) of choice after orthotopic liver transplantation (OLT). Previous studies comparing outcomes with different CNIs used small HCV cohorts or had short-term follow-up. We examined patient survival and fibrosis progression in all HCV-infected adult primary OLT recipients from 1995 to 2004 at the Annette C. and Harold C. Simmons Transplant Institute (n = 516). Patients were categorized by their CNI on day 7 post-OLT, and they were excluded if they died before day 14. Patient and donor age, sex, race, and prevalence of cytomegalovirus infection post-OLT were similar in the tacrolimus and cyclosporine patients. As expected, acute cellular rejection and steroid-resistant rejection were less common in tacrolimus-treated patients. Although no difference in 1-year survival was seen, tacrolimus patients (n = 268) had superior 5-year survival compared to cyclosporine patients (n = 248) (75% vs. 67%; P = 0.02). Fibrosis progression was no different between the groups. In our retrospective analysis of 516 post-OLT patients, tacrolimus improved long-term survival compared to cyclosporine in HCV-infected patients, although it did not impact HCV fibrosis progression.

Renal-sparing immunosuppressive protocol using OKT3 after liver transplantation: a 19-year single-institution experience

Different renal-sparing immunosuppressive protocols have been used in liver transplantation. At our institution, muromonab-CD3 (OKT3) is used in patients with acute renal failure (ARF), along with a delay in starting a calcineurin inhibitor. This study was conducted to compare outcomes in liver transplant patients with ARF who received OKT3 and those who did not. From 1988 to 2007, ARF was present in 1685 of 2587 patients (65%). OKT3 was used in 109 patients (OKT3 group). The control group (1416 patients) received a low-dose calcineurin inhibitor. The OKT3 group was more critically ill. In spite of this, the OKT3 group patients who were on renal replacement therapy (RRT) achieved long-term survival similar to that of the control group on RRT. Among the patients who were not on RRT, the OKT3 group had a higher complete recovery rate, but this did not translate into improved long-term survival. Bacterial and fungal infections were more common in the OKT3 group; however, there was no increased risk of malignancy or death from hepatitis C recurrence. The use of OKT3 in patients with ARF allowed more critically ill patients on RRT to achieve survival rates similar to those of patients who did not receive OKT3.